Subacute Thyroiditis in COVID-19 Patients.

INTRODUCTION: Since December 2019, novel coronavirus (COVID-19) infection has been identified as the cause of an outbreak of respiratory illness in Wuhan, China. The classic presentation of COVID-19 infection was described as fever, myalgia, cough, and fatigue. Whether coronavirus can directly attack the endocrine glands is unclear.
OBJECTIVE: Post-viral subacute thyroiditis (SAT, de Quervain thyroiditis) has been reported following other viral infection. A limited number of SAT after COVID-19 infection have been reported up to now.
METHODS: Here, we reported 6 patients with SAT and positive COVID-19 serology tests. Demographic, clinical, biochemical, and imaging data were presented.
RESULTS: In this study, 6 patients (4 women and 2 men) with clinician manifestations and physical examination in favor of SAT were described. Cervical ultrasonography showed bilateral hypoechoic areas in the thyroid gland which was suggestive of SAT. Elevated C-reactive protein, erythrocyte sedimentation rate, free thyroxine, free tri-iodothyronine, and undetectable thyrotropin were found in laboratory evaluations. Both IgM and IgG were positive for COVID-19 infection, but the PCR tests were negative in all patients. Patients had history of working in a COVID center and/or family member hospitalized due to COVID-19 pneumonia. Patients were followed up for 1 month and were treated effectively with steroids.
CONCLUSION: This report may help physicians to identify lesser-known manifestations and complications of COVID-19. Early diagnosis of COVID-19 infection results in the prevention of further transmission.

In early December 2019, novel coronavirus (COVID-19) infection has been identified as the cause of an outbreak of respiratory illness in Wuhan, China [1]. The World Health Organization declared COVID-19 outbreak as a pandemic as of March 11, 2020 [2].

The classic presentations of COVID-19 infection were described as fever, myalgia, cough, fatigue, and gastrointestinal symptoms such as nausea, vomiting, diarrhea, and abdominal pain [3]. However, different and lesser-known clinical manifestations have also been reported [4, 5, 6]. Whether coronavirus can directly attack the endocrine glands is unclear. Post-viral subacute thyroiditis (SAT, de Quervain thyroiditis) has been reported during outbreaks of other viral infection [7, 8]. Here, we report 6 patients with SAT and positive COVID-19 serology test.

During COVID-19 pandemic 6 patients (4 women and 2 men) were referred to our hospital with same clinical scenarios including fever (more than 38°C), fatigue, palpitations, and anterior neck pain, data of which are presented in Table 1. Patients' physical examination revealed markedly painful, tender, and slightly enlarged thyroid gland. With suspicion to SAT, cervical ultrasonography was performed for each patient. The ultrasonographies showed bilateral hypoechoic areas in thyroid gland which was suggestive of SAT. Laboratory results showed mildly elevated free thyroxine and free tri-iodothyronine with undetectable thyrotropin. C-reactive protein levels were also slightly elevated, and in all patients, erythrocyte sedimentation rate was more than 60 mm/h.

Table 1

Demographic, clinical, and biochemical data in patients with SAT following COVID-19 infection

Patient No./sex/age	Signs, symptoms, and predisposing factor during a month before diagnosis	Biochemical and hormonal data
		at the time of diagnosis		after 1 month
P1/F/26	• History of traveling to a high-prevalence coronavirus area• Self-limited dry cough for 1 week	FT4: 19.5 FT3: 18.9 TSH: 0.07	CRP: 28 ESR: 70 WBC: 12,500	FT4: 17.1 TSH: 2.21ESR: 17
P2/F/37	• She was a nurse at a COVID-19 center• History of a family member's hospitalization due to COVID-19 pneumonia within 2 weeks• Myalgia for few days	FT4:2 2.3FT3: 25.4TSH: <0.01	CRP: 38ESR: 56 WBC: 11,700	FT4: 19.3TSH: 1.83 ESR: 4
P3/M/35	• History of traveling to a high-prevalence coronavirus area• Without symptoms	FT4: 24.7FT3: 19.3 TSH: 0.12	CRP: 18ESR: 45WBC: 9,200	FT4: 13.2TSH: 3.75 ESR: 9
P4/F/41	• History of family member's hospitalization due to COVID-19 pneumonia within 2 weeks• Low-grade fever and mild myalgia for few days	FT4: 21.9FT3: 23.7 TSH: <0.01	CRP: 43ESR: 83 WBC: 14,800	FT4: 18.9TSH: 1.84 ESR: 25
P5/M/52	• History of traveling to a high-prevalence coronavirus area and a family member's hospitalization due to COVID-19 pneumonia within 2 weeks• Low-grade fever, dry cough, and mild myalgia for few days	FT4: 26.7 FT3: 21.6TSH: 0.17	CRP: 51ESR: 76 WBC: 17,600	FT4: 20.1TSH: 0.46 ESR: 28
P6/F/34	• She was a nurse at a COVID-19 center• Without symptoms	FT4: 18.4FT3: 18.1 TSH: 0.23	CRP: 23ESR: 39 WBC: 13,400	FT4: 12.7TSH: 3.67 ESR: 2

Laboratory normal range: FT4: 12–21 pmol/L; FT3: 3.1–6.8 pmol/L; TSH: 0.4 and 4.0 mU/L; CRP: less than 10 mg/L; ESR: 0–22 mm/h for men and 0–29 mm/h for women; WBC: 4,500 to 11,000 counts per microliter. TSH, was measured using an ultrasensitive 3rd generation chemiluminescent assay (sensitivity = 0.01 mIU/L). SAT, subacute thyroiditis; FT4, free thyroxine (pmol/L); FT3, free tri-iodothyronine (pmol/L); TSH, thyrotropin (mU/L); CRP, C-reactive protein (mg/L); ESR, erythrocyte sedimentation rate (mm/h); WBC: white blood cell (count per microliter).

Some patients reported brief, nonspecific symptoms such as low-grade fever and myalgia in the past month prior to their acute presentations, but the symptoms have resolved spontaneously. Two of the patients were nurses at COVID-19 centers. The other 2 had a history of traveling to high-prevalence coronavirus areas. Also 3 out of 6 patients had a history of family members' hospitalization due to COVID-19 pneumonia within 2 weeks. Therefore, PCR and immunoglobulin (IgM and IgG) tests were requested to evaluate COVID-19 infection. The PCR tests were negative in all patients but both IgM and IgG were positive for COVID-19 infection. Serology tests were performed using SARS-CoV-2 (COVID-19) IgG and IgM ELISA kits (BL International GmbH, Flughafenstraße 52a, DE–22335 Hamburg, Germany; IgM REF: 30176470; IgG REF: 30177447).

Their chest computed tomography scans were unremarkable. Patients were treated with prednisolone 25 mg/day for 10 days and were tapered in 4 weeks. After 1 week, the symptoms disappeared and after 1 month thyroid function tests were normal.

To our current knowledge, only few studies in the English-language articles reported SAT in COVID-19 patients [9, 10, 11, 12]. The etiology and pathogenesis of SAT have not been completely understood. SAT can be secondary to viral upper respiratory tract infection in genetically predisposed individuals. Several viruses have been identified as the cause of SAT including, mumps virus, cytomegalovirus, enterovirus, and coxsackie virus [13]. In this study, the screening serology testing for respiratory viral panel, viral hepatitis, mumps virus, cytomegalovirus, Epstein-Barr virus, rubella virus, and human immunodeficiency virus were negative. IgM positivity indicated recent infection with COVID-19 in these series and could confirm the causal relationship.

We believe physicians should be aware of possible different clinical manifestations and complications related to COVID-19 infection. Early screening and diagnosis of COVID-19 infection result in the prevention of further transmission.

Statement of Ethics

The research was carried out according to the principles of the Declaration of Helsinki. Subjects (or their parents or guardians) have given their written informed consent. The local Ethics Review Committee of Tehran University of Medical Science approved the study protocol. Approval ID is IR.TUMS.AMIRALAM.REC.1399.006.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

The authors did not receive any funding.

Author Contributions

Saeed Sohrabpour: collecting data. Farrokh Heidari: writing of the article. Ebrahim Karimi: collecting data. Reza Ansari: collecting data. Firouzeh Heidari: writing and editing of the article. Ardavan Tajdini: Editing of the article.